Acemannan may be a promising therapeutic agent for skin cancer prevention due to its ability to regulate oxidative stress, inflammation, and apoptosis.
Preventive effect of acemannan on DMBA-induced mouse skin tumorigenesis by modulating inflammatory cytokines and apoptosis pathways: molecular docking and molecular dynamic simulation approaches.
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Abstract
Skin cancers, such as melanoma and non-melanoma skin cancers, are increasingly prevalent due to environmental and lifestyle factors. Melanoma arises from the aberrant proliferation of melanocytes and is significantly influenced by UV radiation-induced oxidative stress. This study investigated the therapeutic potential of acemannan against 7,12-dimethylbenz[a]anthracene (DMBA)-evoked skin cancer in mice. Mice were randomly divided (n = 6): a control (group I), DMBA-induced cancer (group II), and two treatment groups (group III&IV) that received acemannan at doses of 25 and 50 mg/kg orally, respectively. After completion of the 14-week treatment protocol, various parameters, including body weight, tumor burden, oxidative stress markers (MDA, ROS), antioxidant enzymes (SOD, CAT, GSH), inflammatory cytokines (IL-6, IL-1β, TNF-α, TGF-β1), p65 subunit of NF-κB signaling, and apoptosis (caspase-3, caspase 9, Bax and Blc2) were assessed. Histopathological examination, molecular docking, and dynamics simulations were also performed. The results demonstrated that acemannan significantly reduced tumor burden, number, and volume in DMBA-treated mice. Acemannan exhibited protective effects by modulating oxidative stress, enhancing antioxidant enzyme activities, suppressing pro-inflammatory cytokines, inhibiting NF-κB signaling, and inducing apoptosis. Molecular docking analysis indicated that acemannan exhibited strong binding affinities to key inflammatory proteins: NFkB, Caspase 3, Caspase 9, TNF-Alpha, BCl2, and BAX, with calculated binding energies of -5.124, -6.631, -5.054, -6.224, -4.33, and -4.425 kcal/mol, respectively. Furthermore, molecular dynamics simulations provided evidence for substantial conformational changes induced by acemannan binding to these proteins. In conclusion, these findings demonstrate that acemannan may be a promising therapeutic agent for skin cancer prevention due to its ability to regulate oxidative stress, inflammation, and apoptosis.
Affiliation
Abdulaziz Ibrahim Alzarea
External References
- PubMed ID:
- 40318716
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